Methanol → N-(2,6-difluorophenyl)-3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamide

HRID 419454Notes

Reaction equation

HRID 419454 reaction equation
[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH2:4].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:20][C:21]1[C:22]([CH2:55][CH2:56][N:57]2[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]2)=[CH:23][C:24]([O:53][CH3:54])=[C:25]([NH:27][C:28]2[N:33]=[C:32]([C:34]3[N:38]4[CH:39]=[CH:40][CH:41]=[CH:42][C:37]4=[N:36][C:35]=3[C:43]3[CH:44]=[C:45]([CH:50]=[CH:51][CH:52]=3)[C:46](OC)=[O:47])[CH:31]=[CH:30][N:29]=2)[CH:26]=1.CO>C1COCC1>[F:1][C:2]1[CH:8]=[CH:7][CH:6]=[C:5]([F:9])[C:3]=1[NH:4][C:46](=[O:47])[C:45]1[CH:50]=[CH:51][CH:52]=[C:43]([C:35]2[N:36]=[C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][N:38]3[C:34]=2[C:32]2[CH:31]=[CH:30][N:29]=[C:28]([NH:27][C:25]3[CH:26]=[C:21]([F:20])[C:22]([CH2:55][CH2:56][N:57]4[CH2:62][CH2:61][CH2:60][CH2:59][CH2:58]4)=[CH:23][C:24]=3[O:53][CH3:54])[N:33]=2)[CH:44]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 796472,6-DifluoroanilineHCID 2724254Sodium bis(trimethylsilyl)amideHCID 59452635Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl]amino)-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl}benzoate

Product 1

HCID 59452598N-(2,6-difluorophenyl)-3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzamideYield 37.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 2,6-difluoroaniline (133 mg, 1 mmol) was added 1N NaHMDS in THF (1 mL, 1 mmol). The mixture stirred for 15 min at rt. Methyl 3-{3-[2-({5-fluoro-2-(methyloxy)-4-[2-(1-piperidinyl)ethyl]phenyl}amino)-4-pyrimidinyl]imidazo[1,2-a]pyridin-2-yl}benzoate (120 mg, 0.206 mmol) in 3 mL of dry THF was added. The mixture stirred at rt for 30 min. 1 mL of MeOH was added followed by 1 g of silica gel. The solvent was rotovaped down and the pre-adsorbed solids were purified by flash chromatography to give the title compound (52 mg, 0.0767 mmol, 37%). 1H NMR (400 MHz, CDCl3) δ ppm 9.46 (d, J=7.33 Hz, 1H), 8.21-8.29 (m, 3H), 8.11 (s, 1H), 8.02 (d, J=7.70 Hz, 1H), 7.74-7.83 (m, 2H), 7.66 (d, J=8.80 Hz, 1H), 7.47-7.56 (m, 1H), 7.32-7.40 (m, 1H), 7.22 (dd, J=8.43, 5.87 Hz, 1H), 6.91-7.01 (m, 3H), 6.76 (d, J=6.60 Hz, 1H), 6.63 (dd, J=5.32, 3.12 Hz, 1H), 3.92 (s, 3H), 2.79-2.87 (m, 2H), 2.54-2.61 (m, 2H), 2.45-2.54 (m, 4H), 1.59-1.68 (m, 4H), 1.42-1.52 (m, 2H). MS (ESI): 678 [M+H]+.

Workup

  1. stirringThe mixture stirred at rt for 30 min
  2. customthe pre-adsorbed solids were purified by flash chromatography

Sources & evidence

ORD record
ord-4ee053d7ae9d42eca66dbf2819ea19eb
Source dataset
uspto-grants-2012_01
Patent number
US08093239B2

Reaction notes

Loading…